Cisplatin / 5-Fluorouracil for Vulval Cancer

Transcription

1 Cisplatin / 5-Fluorouracil for Vulval Cancer Indication: Palliative therapy in patients with Vulval Cancer Regimen details: Cisplatin 75mg/m 2 (*) IV 5-Fluorouracil (5-FU) 1000mg/m 2 /24 hours IV D4 (*)Consider starting Cisplatin at 60mg/m 2 in patients with reduced performance status. Increase dose to 75mg/m 2 with second cycle only if well tolerated Administration: Furosemide 40mg orally 1 litre Sodium Chloride 0.9% + 20mmol KCl + 1g Mg SO 4 IV infusion over 60 minutes Cisplatin in 1000ml Sodium Chloride 0.9% over 2 hours 1 litre Sodium Chloride 0.9% + 40mmol KCl + 1g Mg SO 4 IV infusion over 2 hours Then either 500ml Sodium Chloride 0.9% IV infusion over 60 minutes or 500ml drinking water *Follow guidance protocol for Hydration schedules & fluid balance monitoring for outpatient Cisplatin regimens Any device containing aluminium that may come in contact with Cisplatin must be avoided 5-FU infusion either via central venous catheter and ambulatory infusion device (this may be attached on the afternoon of Day 1, after the Cisplatin and post-hydration have completed) OR Continuous peripheral IV infusion over 96 hours (4 days) (this administration method requires an inpatient admission for the duration of the infusion), given in 4 x 1 litre Sodium Chloride 0.9% (Cisplatin, hydration and any other IV drugs to be administered via a second peripheral cannula) Frequency: Extravasation: Anti- emetics: Supportive medication: Every 21 days, for a maximum of 6 cycles Cisplatin and 5FU: Non-vesicants : Highly emetogenic D2 D4: Low emetogenic Follow Local Antiemetic Policy Patients may require: Loperamide tablet/caps 4mg stat, then 2mg PRN for diarrhoea Pyridoxine tablets 50mg po tds, if required for palmar-plantar erythema (PPE) Mouthwashes, when required- refer to local mouthcare guidelines Regular investigations: FBC U&Es LFTs Mg 2+ and Ca 2+ EDTA Prior to 1 st cycle Audiogram Prior to 1 st cycle if clinically indicated CT scan (disease evaluation) After 3 cycles, Page 1 of 5

2 Comments: Hydration - Cisplatin Encourage oral hydration during treatment; for instance, drink a glass of water every hour during treatment, and at least a further 2 litres over the 24 hours following treatment Weight should be recorded prior to and at the end of Cisplatin treatment, and a strict fluid balance chart should be maintained. An average urine output of at least 100ml/hr must be maintained throughout treatment, and Cisplatin infusion should not be commenced unless this urine output is achieved. For low urine output, consider increasing the pre-hydration and diuretic regimen. Consider adding diuretics in weight-gain of 1.5 kg, or symptoms of fluid overload Allergy Cisplatin Anaphylactic-like reactions to Cisplatin have been reported. Facial edema, bronchoconstriction, tachycardia and hypotension may occur within minutes of Cisplatin administration. Adrenaline, corticosteroids and antihistamines have been effectively employed to alleviate symptoms. No further Cisplatin should be given unless within a desensitising protocol Electrolyte disturbances Cisplatin Disturbances in electrolytes can be a long term manifestation due to the Cisplatin induced renal tubular dysfunction. Check electrolytes- additional supplementation of magnesium, calcium or potassium may be required Cardiotoxicity 5-Fluorouracil Cardiotoxicity has been associated with fluoropyrimidine therapy, including myocardial infarction, angina, dysrhythmias, cardiogenic shock, sudden death and electrocardiographic changes. These adverse events may be more common in patients with a prior history of coronary artery disease. Caution must be exercised in patients with history of significant cardiac disease, arrhythmias and angina pectoris Coronary artery spasm is more common in patients receiving continuous infusions of 5FU and is usually reversible on discontinuing the infusion. Should a patient receiving 5FU present with chest pains, stop the 5FU. Standard investigation and treatment of angina may be required. If rechallenge is necessary, this can be performed under Consultant supervision, but should symptoms redevelop, the 5FU should be withdrawn permanently DPD deficiency 5-Fluorouracil Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe toxicity secondary to reduced metabolism of fluorouracil, usually manifest as severe toxicity within days of administration. If patients complain of toxicity very soon after administration, it is important to ensure supportive measures are implemented as soon as possible and Consultant consulted before further doses prescribed Page 2 of 5

3 DOSE MODIFICATIONS Haematological Toxicity WBC < 3.0 x 10 9 /L or Neutrophils < 1.5 x 10 9 /L or Platelets < 100 x 10 9 /L Delay Chemotherapy for 1 week. Repeat FBC If within normal parameters, proceed with 100% doses. Subsequent cycles If Neutrophils < 0.5 x 10 9 / L for 7 days, OR Febrile neutropenia is diagnosed OR Platelets < 50 x 10 9 /L for 7 days, Cisplatin should be reduced to 80% from previous Cisplatin dose (60mg/m 2 from 75mg/m 2 OR 50mg/m 2 from 60mg/m 2 ) and 5-Fluorouracil should be given at 75% dose (750mg/m 2 from 1000mg/m 2 ). Do not escalate for subsequent cycles If patient has repeated delays, abandon chemotherapy at Consultant s discretion Renal Impairment: GFR should be calculated using the Cockcroft & Gault equation in all patients; if the calculated GFR < 60 or > 120ml/min, measure EDTA clearance or creatinine clearance before prescribing. Monitor trends in serum creatinine between treatments: if 20% from baseline value, re-calculate GFR using the Cockcroft & Gault equation 5FU: Consider dose reduction in severe renal impairment (GFR < 10ml/min) only Cisplatin induces nephrotoxicity, which is cumulative. It is therefore contraindicated in patients with renal impairment. Consider dose reduction following the table below: CrCl (ml/min) Cisplatin Dose > 60 Give 100% Give 80% < 50 Contraindicated Hepatic Impairment Cisplatin: No dose reduction necessary Fluorouracil should be used with caution in patients with reduced liver function or jaundice: Bilirubin (µmol/l) AST 5FU Dose < 85 < 180 Give 100% > 85 or > 180 Contraindicated Page 3 of 5

4 DOSE MODIFICATIONS FOR OTHER TOXICITIES AS APPROPRIATE NEUROPATHY/ OTOTOXICITY CISPLATIN Cisplatin induced neuropathy is cumulative : Grade Neuropathy-sensory Ototoxicity Cisplatin Dose 1 Paresthesia (including tingling) but not Give 100% interfering with function 2 Paresthesia interfering with function, Tinnitus not interfering with Give 80% but not interfering with activities of daily living activities of daily living 3 Paresthesia interfering with activities of Tinnitus interfering with Omit Cisplatin daily living activities of daily living 4 Disabling Disabling Omit Cisplatin Toxicities: Myelosuppression; fatigue; nausea; vomiting; constipation; diarrhoea; mucositis; stomatitis; nephrotoxicity; neuropathy / ototoxicity; taste disturbance; electrolyte disturbances; allergic reactions; cardiotoxicity; palmar-plantar erythema (PPE); alopecia Drug interactions: Cisplatin -Allopurinol, colchicine, probenecid, sulfinpyrazone : increase in serum uric acid concentration -Cephalosporins, aminoglycosides, amphotericin B : increase nephrotoxic and ototoxic effects of Cisplatin in these organs -Ciclosporine : excessive immunosuppression, with risk of lymphoproliferation -Cyclizine, phenothiazines : may mask ototoxicity symptoms -Furosemide (high doses), hydralazine, diazoxide and propranolol : intensify nephrotoxicity -Oral anticoagulants : require an increased frequency of the INR monitoring -Penicillamine : may diminish the effectiveness of Cisplatin -Phenytoin : reduced epilepsy control Fluorouracil -Allopurinol : avoid concomitant use -Clozapine : increased risk of agranulocytosis, avoid concomitant use -Coumarins : enhanced anticoagulant effect -Digoxin tablets : reduced absorption (resolved by giving the digoxin in liquid) -Leucovorin : increased cytotoxic and toxic effects of Fluorouracil -Metronidazole ; Cimetidine : inhibit metabolism of fluorouracil (increased toxicity) -Phenytoin : reduced absorption of the antiepileptic -Sorivudine : marked and rapidly fatal fluorouracil toxicity Page 4 of 5

5 References: Summary of Product Characteristics. Cisplatin. Wockhardt UK Ltd. September 2006 Summary of Product Characteristics. Fluorouracil. Medac GmbH.February 2007 Salom EM et al. Curr Treat Options Oncol (2002); 3 (2): COIN guidelines, October 2000 Hydration schedules & fluid balance monitoring for outpatient Cisplatin regimens. Mar 06 Practical Chemotherapy. A multidisciplinary guide. Summerhayes M. et al Cisplatin dosage adjustment in Renal Impairment. Personal communication with Dr. A. Winship. Aug 09 UCLH- Dosage Adjustment for Cytotoxics in Renal Impairment. November 2003 UCLH- Dosage Adjustment for Cytotoxics in Hepatic Impairment. November 2003 GSTT guidelines for treating nausea and vomiting in adult patients. September 2007 SELCN Cytotoxic Extravasation Guidelines. Draft July 2008 Stockley s Drug Interactions. Interactions search: Cisplatin&Fluorouracil.July 08 CTCAE v3.0. August 2006 Page 5 of 5